Porphyromonas gingivalis is an important etiologic agent of periodontal diseases. It is estimated that over 49,000,000 people in the United States have some form of periodontitis (Cutler et al., Trends Microbiol. 3:45 (1995)). Periodontitis occurs with higher frequency in patients with systemic disease such as diabetes mellitus, AIDS, leukemia, neutropenia, Crohn's disease, and Down's syndrome (Neville et al., Oral and Maxillofacial Pathology. Philadelphia: Saunders, 1995). Currently, standard microbiological tests for Pg detect only the presence of Pg in dental plaque, but do not specifically identify disease activity. For this reason, these tests have a low positive predictive value. Because Pg is normally found in plaque of even healthy individuals, the application of these tests is limited in their usefulness to those who present with certain clinical manifestations of disease. These include the following: 1) patients with advanced attachment loss and bone loss before the age of 25; 2) Patients, usually aged 25-35, with rapid destruction of attachment and bone in a relatively short period of time (rapidly progressive periodontitis); 3) patients who continue to lose attachment despite stringent treatment (refractory periodontitis); and 4) patients older than 35 who have a slow rate of attachment loss.
Diagnostic tests are needed in the art for other types of patients including, for example: 1) certain preadolescent children whose mothers have a history of periodontitis who are in need of tests that will determine if thy have acquired a predisposition for the disease, including, for example, Papillon-Lefevre syndrome (PLS), hypophosphatasia, neutropenias, leukocyte adhesion deficiency (LAD), Chediak-Higashi syndrome, Down's syndrome, leukemia, histiocytosis X, early-onset Type 1 diabetes, and acrodynia; 2) other preadolescent children who are less prone would also benefit from such a test since there are no other predictors or known risk factors; 3) adults already diagnosed or not yet diagnosed would benefit from knowing whether or not they have Pg present that are disease primed.
A national survey of the United States revealed a prevalence of localized juvenile periodontitis of 0.53% and of generalized juvenile periodontitis of 0.13%. Loe & Brown, J. Periodontol. 62:608-616 (1991). Findings from a number of studies corroborate the conclusion that early-onset disease is similar in other industrialized countries and is more frequent in developing countries. Loe & Brown, J. Periodontol. 62:608-616 (1991). In addition, certain types of adult periodontitis, which in general is a very common condition affecting over half of the adult population, are likely to be cased by Pg. In short, a good diagnostic for Pg induced periodontal disease could became a standard operating procedure for dental practitioners worldwide. In should be noted that Pg can also cause extra-oral diseases such as endocarditis, thyroid gland abscesses, urinary tract infections, brain abscesses, and vertebral osteomyelitis.
There are antibiotic, surgical, and mechanical therapies for the treatment of Pg induced periodontitis, but no means for prevention. Tetracycline has been widely used in the treatment of early-onset periodontitis. There remains a concern, however, of strains developing resistance to tetracycline as well as the possibility of overgrowth of other pathogenic microorganisms subgingivally. Given the incidence of these diseases, a safe vaccine for Pg is needed. A vaccine can be, for example, a multivalent vaccine. Control of periodontal disease is also very important in light of recent attention to the possible role of periodontal infections as risk factors for systemic disease (e.g., coronary heart disease).
No significant advances in the diagnosis, treatment or prevention of periodontal diseases have occurred in the past three decades since antibiotic regimens were adopted. DNA probe technology and immunoassay technology has been developed to identify the presence of Pg in dental plaque, but these technologies are unable to distinguish between the Pg that is normally part of the dental plaque community and Pg that is involved in an actual disease process. Consequently, those dentists who use these technologies recognize that they do not provide a “gold standard” for diagnosing disease activity.
Early diagnosis of periodontitis is highly desirable. Currently, diagnosis is made by X-ray analysis usually long after the onset of the disease and after considerable damage to the supporting bone and tissue has occurred. Tooth loss is the ultimate detrimental effect of destructive periodontal disease. Most people have Pg as a normal member of their dental plaque, but it usually does not cause disease. When Pg does cause disease the human host mounts an enormous response but it is inevitably futile presumably because it is directed against the wrong Pg antigens.
Prevention is much preferred in medicine to treatment. Currently, the prevalence and severity of early-onset periodontal diseases is addressed with a combination of mechanical plaque removal and a variety of systemic and topically applied antimicrobial agents aimed at selectively removing or inhibiting pathogenic bacteria. An effective vaccine against Pg would effectively reduce the use of antibiotics to control the destructive aspects of the early-onset periodontal diseases.
Compared to the number of different infectious diseases, there are relatively few reliable diagnostic tests and vaccines. In large part this is because pathogens regulate expression of their genes that are essential to the disease process: important environmental signals that normally cause the bacteria to turn on virulence genes during an infection are missing when they are grown in the laboratory. Consequently, many of the best targets for diagnostic and vaccine strategies remain unknown.